Abstract：
OBJECTIVE: We investigated the effect of 52-week treatment with liraglutide, a glucagon-like peptide 1 receptor agonist, on glucose tolerance and incretin effect in women with previous gestational diabetes mellitus (pGDM).
METHODS: Women with overweight/obesity and pGDM were randomized to once daily subcutaneous liraglutide 1.8 mg or placebo for 52 weeks. Participants underwent oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion at baseline and at 52 weeks, and an additional OGTT after the drug wash-out.
RESULTS: In total, 104 women [age: mean ± SD, 38 ± 5 years; fasting plasma glucose (FPG): 5.5 ± 0.4 mmol/L; glycated haemoglobin (HbA1c): 33 ± 4 mmol/mol, bodyweight: 88.2 ± 14.8 kg, body mass index: 31.1 ± 4.3 kg/m2 ] were assigned to liraglutide (n = 49) or placebo (n = 55). Estimated treatment difference (ETD) for area under curve during OGTT was -173 (95% confidence interval -250 to -97) mmol/L × min, p < .0001, but after wash-out the difference disappeared [ETD 58 (-30 to 146) mmol/L × min, p = .536]. Liraglutide reduced FPG [ETD -0.2 (-0.4 to -0.1) mmol/L, p = .018], HbA1c [-2.2 (-3.5 to -0.8) mmol/mol, p = .018] and bodyweight [-3.9 (-6.2 to -1.6) kg, p = .012]. No change in the incretin effect was observed. The number of women with prediabetes was reduced from 64% to 10% with liraglutide vs. 50% with placebo [adjusted odds ratio 0.10 (0.03-0.32), p = .002].
CONCLUSIONS: Treatment with liraglutide for 52 weeks improved glucose tolerance, FPG, HbA1c and bodyweight in women with overweight/obesity and pGDM. Progression to prediabetes while on drug was markedly reduced, but after a 1-week drug wash-out, the effect was lost.
METHODS: Women with overweight/obesity and pGDM were randomized to once daily subcutaneous liraglutide 1.8 mg or placebo for 52 weeks. Participants underwent oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion at baseline and at 52 weeks, and an additional OGTT after the drug wash-out.
RESULTS: In total, 104 women [age: mean ± SD, 38 ± 5 years; fasting plasma glucose (FPG): 5.5 ± 0.4 mmol/L; glycated haemoglobin (HbA1c): 33 ± 4 mmol/mol, bodyweight: 88.2 ± 14.8 kg, body mass index: 31.1 ± 4.3 kg/m2 ] were assigned to liraglutide (n = 49) or placebo (n = 55). Estimated treatment difference (ETD) for area under curve during OGTT was -173 (95% confidence interval -250 to -97) mmol/L × min, p < .0001, but after wash-out the difference disappeared [ETD 58 (-30 to 146) mmol/L × min, p = .536]. Liraglutide reduced FPG [ETD -0.2 (-0.4 to -0.1) mmol/L, p = .018], HbA1c [-2.2 (-3.5 to -0.8) mmol/mol, p = .018] and bodyweight [-3.9 (-6.2 to -1.6) kg, p = .012]. No change in the incretin effect was observed. The number of women with prediabetes was reduced from 64% to 10% with liraglutide vs. 50% with placebo [adjusted odds ratio 0.10 (0.03-0.32), p = .002].
CONCLUSIONS: Treatment with liraglutide for 52 weeks improved glucose tolerance, FPG, HbA1c and bodyweight in women with overweight/obesity and pGDM. Progression to prediabetes while on drug was markedly reduced, but after a 1-week drug wash-out, the effect was lost.
摘要：
目的：我们研究了利拉鲁肽治疗52周的效果，胰高血糖素样肽1受体激动剂，先前妊娠糖尿病（pGDM）妇女的糖耐量和肠促胰岛素作用。
方法：超重/肥胖和pGDM的女性随机分为每天一次皮下利拉鲁肽1.8mg或安慰剂，共52周。参与者在基线和52周时接受口服葡萄糖耐量试验（OGTT）和等值葡萄糖静脉输注，和药物冲洗后的额外OGTT。
结果：总计，104名妇女[年龄：平均值±SD，38±5年；空腹血糖（FPG）：5.5±0.4mmol/L；糖化血红蛋白（HbA1c）：33±4mmol/mol，体重：88.2±14.8kg，体重指数:31.1±4.3kg/m2]被分配给利拉鲁肽(n=49)或安慰剂(n=55).OGTT期间曲线下面积的估计治疗差异（ETD）为-173（95％置信区间-250至-97）mmol/L×min，p<.0001，但冲洗后差异消失[ETD58（-30至146）mmol/L×min，p=.536]。利拉鲁肽降低FPG[ETD-0.2（-0.4至-0.1）mmol/L，p=.018],HbA1c[-2.2（-3.5至-0.8）mmol/mol，p=.018]和体重[-3.9(-6.2至-1.6)kg,p=.012]。没有观察到肠促胰岛素作用的变化。与利拉鲁肽相比，患有前驱糖尿病的女性人数从64％减少到10％安慰剂的50％[调整后的赔率比0.10（0.03-0.32），p=.002]。
结论：利拉鲁肽治疗52周可改善糖耐量，FPG,超重/肥胖和pGDM女性的HbA1c和体重。在药物治疗期间，糖尿病前期的进展明显减少，但是经过一周的药物清洗后，效果消失了。
方法：超重/肥胖和pGDM的女性随机分为每天一次皮下利拉鲁肽1.8mg或安慰剂，共52周。参与者在基线和52周时接受口服葡萄糖耐量试验（OGTT）和等值葡萄糖静脉输注，和药物冲洗后的额外OGTT。
结果：总计，104名妇女[年龄：平均值±SD，38±5年；空腹血糖（FPG）：5.5±0.4mmol/L；糖化血红蛋白（HbA1c）：33±4mmol/mol，体重：88.2±14.8kg，体重指数:31.1±4.3kg/m2]被分配给利拉鲁肽(n=49)或安慰剂(n=55).OGTT期间曲线下面积的估计治疗差异（ETD）为-173（95％置信区间-250至-97）mmol/L×min，p<.0001，但冲洗后差异消失[ETD58（-30至146）mmol/L×min，p=.536]。利拉鲁肽降低FPG[ETD-0.2（-0.4至-0.1）mmol/L，p=.018],HbA1c[-2.2（-3.5至-0.8）mmol/mol，p=.018]和体重[-3.9(-6.2至-1.6)kg,p=.012]。没有观察到肠促胰岛素作用的变化。与利拉鲁肽相比，患有前驱糖尿病的女性人数从64％减少到10％安慰剂的50％[调整后的赔率比0.10（0.03-0.32），p=.002]。
结论：利拉鲁肽治疗52周可改善糖耐量，FPG,超重/肥胖和pGDM女性的HbA1c和体重。在药物治疗期间，糖尿病前期的进展明显减少，但是经过一周的药物清洗后，效果消失了。
